Acta Tropica 74 (2000) 229–234 Proinflammatory cytokine mRNA responses in experimental Burkholderia pseudomallei infection in mice Glen C. Ulett a, *, Natkunam Ketheesan b , Robert G. Hirst a a Department of Microbiology and Immunology, James Cook Uniersity, Townsille, Queensland 4811, Australia b Department of Medicine, North Queensland Clinical School, Uniersity of Queensland, Queensland 4810, Australia Abstract Melioidosis is a potentially fatal disease of both human and animals caused by the bacterium Burkholderia pseudomallei. Disease is endemic in tropical and subtropical regions of Southeast Asia and Northern Australia. The pathogenesis of melioidosis is poorly understood. In particular, the host responses that occur following infection, and the specific host-pathogen interactions that result in the development of either acute or chronic infection are unclear. Using an established murine model, we investigated early proinflammatory cytokine responses believed to be critical in the development of acute and chronic B. pseudomallei infection. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to assess levels of mRNA for tumor necrosis factor- (TNF-), interleukin 1 (IL-1) and interleukin 6 (IL-6) in the liver of mice following infection. We demonstrate that the level of mRNA for these cytokines increase moderately in chronic infection in C57BL/6 mice. However, in acute infection in BALB/c mice, mRNA responses for these cytokines were shown to be comparatively greater. These results demonstrate that early proinflammatory cytokine responses are important in the immunopathogenesis of melioidosis. © 2000 Elsevier Science B.V. All rights reserved. Keywords: Burkholderia pseudomallei ; Melioidosis; Cytokine; C57BL/6; BALB/c; mRNA www.elsevier.com/locate/actatropica 1. Introduction Melioidosis, a life-threatening disease affecting both human and animals, comprises a broad spec- trum of disease presentations resulting from infec- tion with the gram-negative bacterium Burkholderia pseudomallei. At the poles of the spectrum are the acute and chronic forms of disease (Smith et al., 1987; Leelarasamee and Bovornkitti, 1989; Chaowagul et al., 1993). Acute disease is often septicaemic and can result in death within days of exposure. In contrast, chronic infection can occur asymptomatically and may persist for many years. Other than the premise that infection occurs subcutaneously or via ingestion/inhalation, little is known regarding the pathogenesis of melioidosis (Smith et al., 1987; Leelarasamee and Bovornkitti, 1989; Hirst et al., 1992; Leakey et al., 1998). The im- munopathogenesis of melioidosis, with particular respect to the development of acute versus chronic * Corresponding author. Tel.: +61-7-47816876; fax: +61-7- 47791526. E-mail address: glen.ulett@jcu.edu.au (G.C. Ulett) 0001-706X/00/$ - see front matter © 2000 Elsevier Science B.V. All rights reserved. PII:S0001-706X(99)00075-3